Changes in serum levels of M30, M65, and IL-17 and their clinical significance in patients with acute pancreatitis / 临床肝胆病杂志

ObjectiveTo investigate the changes in serum levels of M30, M65, and interleukin-17 (IL-17) and their clinical significance in patients with acute pancreatitis. MethodsA total of 126 patients with acute pancreatitis who were admitted to our hospital from December 2009 to December 2013 were selected, and according to clinical diagnosis, they were divided into mild acute pancreatitis group (82 patients) and severe acute pancreatitis group (44 patients). A total of 107 healthy subjects who underwent physical examination during the same period of time were enrolled as the control group. On days 1, 2, and 4, the serum levels of M30, M65, and IL-17 were measured, and M30/M65 ratio was calculated. Comparison of coutinous data between multiple groups was made by ANOVA and pairwise comparison between any two groups was made by SNK-q test, comparison between two groups was made by independent-sample t test, while comparison of categorical data by chisquare test. ResultsOn days 1, 2, and 4, the severe acute pancreatitis group and mild acute pancreatitis group had significantly higher serum levels of M30, M65, and IL-17 (P＜0.05), and a significantly lower M30/M65 ratio (P＜0001), as compared with the healthy controls. On days 1, 2, and 4, the severe acute pancreatitis group had significantly higher serum levels of M30 and M65 than the mild acute pancreatitis group (P＜0.001); on day 1, the severe acute pancreatitis group had a significantly lower M30/M65 ratio than the mild acute pancreatitis group (P＜0.001); the serum level of IL-17 showed no significant difference between the two groups (P＞0.05). M65 and IL-17 had high sensitivity and specificity in the diagnosis of acute pancreatitis. ConclusionThe serum levels of M65 and IL-17 and M30/M65 ratio at 24 hours after the attack of acute pancreatitis can be used as the serological biomarkers for early evaluation of the severity of acute pancreatitis.

Prognostic value of keratin 18 for the patients with hepatitis B virus-related acute-on-chronic liver failure / 中华传染病杂志

Objective To analyze the serum keratin 18 (K18) level of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) and its correlation with prognosis.Methods From December 2012 to October 2014,120 patients who visited Fuzhou Infectious Diseases Hospital and diagnosed with HBV-ACLF were enrolled,and 20 chronic hepatitis B (CHB) patients and 20 healthy controls were enrolled with matched gender and age.Enzyme linked-immunosorbent assay was used for the detection of K18 (M30,M65) and the differences of M30,M65,M30/M65 and other laboratory results were analyzed among the first enrolled 40 patients with HBV-ACLF,20 CHB patients and 20 healthy controls.All HBV-ACLF patients were followed up for 3 months and divided into two groups (death group and survival group).And M30 and M65 in both groups were detected and their clinical data were collected.Continuous variables between groups were compared using t test and one-way analysis of varicmce.Categorical variables were compared using X2 test.Receiver operating characteristic (ROC) curve was used for prognostic analysis.Results The serum M30 in HBV-ACLF group,CHB group and healthy controls group were (2.99 ±0.29),(3.12±0.26) and (2.16 ±0.12) lg U/L,respectively (F=95.36,P＜ 0.01).The serum M65 in the three groups were (3.41 ± 0.29),(3.38+0.29) and (2.01±0.11) lg U/L,respectively (F=217.60,P＜0.01).And M30/M65 the three groups were 0.39 ± 0.11,0.55 ± 0.09 and 1.45 ± 0.34,respectively (F=202.63,P＜0.01).The white blood cell,total bilirubin,alanine aminotransferase and aspartate aminotransferase in HBV-ACLF patients were the highest,and platelet,albumin,serum sodium and prothrombin time activity were the lowest.After following up for 3 months of 120 patients with HBV-ACLF,40 of them died with fatality rate of 33.3％.The area under ROC curve (AUC) of the M30/M65 was 0.871,and that of score of model for endstage liver disease (MELD) was 0.668 (Z=3.011,P＜0.01).The M30/M65 ratio was significantly negatively correlated with the MELD score (r=-0.389,P＜0.01).Conclusions K18 (M65 and M30)are strongly associated with liver disease severity.The M30/M65 ratio may be a potential diagnostic and prognostic marker for the patients with HBV-ACLF.

Expression and its clinical significance of cytokeratin 18 and Fas in nonalcoholic fatty liver disease / 中华消化杂志

Objective To assess the diagnostic value of cytokeratin 18 fragment M30 (CK18-M30) and Fas in patients with nonalcoholic fatty liver disease (NAFLD),especially nonalcoholic steatohepatitis (NASH).Methods Among 58 patients with NAFLD,36 patients with NAFLD received liver biopsy.According to NAFLD activity score (NAS) and liver fibrosis score,patients were divided into NASH group (24 cases) and non-NASH group (12 cases).And at the same period,15 healthy individuals were set as healthy control group.The serum level of CK18 M30 and Fas were measured with enzyme-linked immunosorbant assay (ELISA).Rank sum test was performed to analyze the differences in the level of CK18-M30 and Fas between groups.The diagnostic value of CK18 M30 and Fas were assessed by the receiver operating characteristic (ROC) curves.Results The level of serum CK18-M30 of NAFLD group was significantly higher than that of healthy control group (97.24 U/L (86.06 to 113.12 U/L) vs 78.41 U/L (74.29 to 80.76 U/L),Z=-4.206,P＜0.01)).The level of serum CK18-M30 of NASH group was higher than that of non-NASH group (111.06 U/L (94.30 to 142.68 U/L) vs 89.00 U/L (83.56 to 106.50 U/L),Z=-2.233,P＜0.05)).The area under the ROC curve (AUC) of CK18-M30 in the diagnosis of NASH was 0.73 (0.56,0.90),and the sensitivity and specificity of CK18-M30 in diagnosis of NASH was 79.2％ and 58.3％,respectively.The AUC of Fas in diagnosis of NASH was 0.58 (0.38,0.77),while the sensitivity and specificity of Fas in diagnosis of NASH was 54.2％ and 66.7 ％.The serum level of Fas increased in FAFLD group compared with healthy control group,and in NASH group compared with non-NASH group,however the differences were not signifincant (both P＞ 0.05).Conclusions The level of CK18-M30 has certain value in the diagnosis of NASH.The diagnostic value of Fas in NASH needs more samples in further study.

Relationship between cytokeratin 18 phosphorylation and hepatitis B virus infection / 中华传染病杂志

Objective To investigate the relationship between hepatitis B virus (HBV) infection and cytokeratin 18 (CK18) phosphorylation.Methods Liver tissues were taken from 21 chronic hepatitis B (CHB) patients by liver biopsy and 14 healthy controls were collected.Immunofluorescence double staining and Western blotting were used to detect CK18 pSer33 and CK18 pSer52 phosphorylation.HepG2 cell line was transfected with either 1.3 mer HBV vector or empty control vector.CK18 pSer33 or CK18 pSer52 phosphorylation were tested using immunofluorescence double staining and Western blotting.Total mRNA was extracted from the cells.The expressions of cell division cycle 2 (cdc2) and protein kinase Cε (pKCε) were analyzed by realtime polymerase chain reaction relative quantification.Statistical analyzee were performed by using two-independent samples t test.Results Compared to healthy controls,phosphorylation of CK18 pSer33 in HBsAg stained hepatocytes was significantly higher in CHB patients (t=6.618,P=0.000).However,no difference was found in phosphorylation of pSer52 (t=2.429,P=0.051).Phosphorylation of CK18 pSer33 and expression of cdc2 mRNA in HBV transfected HepG2 were significantly higher in empty vector transfected HepG2 (t=5.365,P=0.006),while no difference was found in phosphorylation of pSer52 and expression of pKCε mRNA (t=1.098,P=0.334).Conclusion HBV infection is significantly associated with phosphorylation of CK18 pSer33.

Progress on serum levels of keratin-18 fragments in chronic hepatitis B and perspective of its application / 中华临床感染病杂志

The diagnostic value of keratin-18 and its fragments in liver diseases has drawn increasingly interests in recent years,but studies on its application in chronic hepatitis B is still few.This paper reviews the circulating levels of keratin-18 fragments M30 and M65 in chronic hepatitis B and its application in the future.

Clinical Correlation between Serum Cytokeratin-18 and Metabolic Parameters in Patients with Sonographic Non-alcoholic Fatty Liver Disease / 대한소화기학회지

BACKGROUND/AIMS: The serum cytokeratin-18 (CK-18) has been suggested to be a surrogate marker of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the correlation between CK-18 and metabolic parameter in NAFLD patients. Correlation between CK-18 and macronutrient composition was also assessed. METHODS: A total of 212 subjects were recruited. Blood chemistry including fasting glucose, cholesterol level, AST, ALT, and CK-18 were compared. Data on calorie intake and carbohydrate consumption were acquired by five-day-diet diary using 24 hour recall method. RESULTS: Plasma CK-18 were markedly increased in patient with NAFLD compared with control group (420.4+/-282.3 vs. 313.6+/-179, p<0.001). Plasma CK-18 were positively correlated with systolic blood pressure (r=0.130), ALT (r=0.503) and negatively correlated with HDL cholesterol (r=-0.246). NAFLD patients with metabolic syndrome had higher CK-18 level than those without metabolic syndrome (484.0 vs. 372.1 U/L, p=0.021). When NAFLD patients were subdivided into two groups with CK-18 cut-off value of 400 U/L, patients with CK-18 level over 400 U/L showed higher body mass index (28.0+/-4.5 vs. 25.5+/-4.3), subcutaneous abdominal fat (283.5+/-172.2 vs. 195.7+/-147.8), AST (52.7+/-26.3 vs. 40.7+/-23.5) and ALT (102.0+/-52.6 vs. 61.2+/-32.2). Calorie intake (r=0.301) and carbohydrate intake (r=0.305) also showed positive correlation with CK-18. CONCLUSIONS: Plasma CK-18 showed positive correlation with metabolic parameters as well as calorie and carbohydrate intake when its cut-off value of greater than 400 U/L was used.

The diagnosis value of a new tumor marker CK18-3A9 serum level for gastric cancer / 肿瘤研究与临床

Objective To investigate the diagnosis value of a new tumor marker CK18-3A9 in gastric cancer patients. Methods The serum level of CK18-3A9 in 350 gastric cancer patients, 150 gastritis patients and 500 healthy controls was detected with chemoluminescence, the diagnosis efficacy between the serum CK18-3A9 and CA72-4 was compared. Results The sensitivity, specificity of CK18-3A9 were 46.29 % and 96.92 %, but the sensitivity, specificity of CA72-4 were 26.00 % and 93.23 %, respectively. The differences were significant (P ＜0.001). Conclusion The serum level of CK18-3A9 maybe a new auxiliary diagnosis marker for gastric cancer.

Clinical application of serum tissue polypeptide-specific antigen detection in diagnosis of alcoholic hepatitis / 国际检验医学杂志

Objective To investigate the role of serum tissue polypeptide-specific antigen (TPS)detection in the evaluation of hepatocyte apoptosis in patients with alcoholic hepatitis and to further evaluate its application in the differential diagnosis of alcoholic hepatitis and fatty liver. Methods The automatic biochemistry analyzer was employed to detect common markers for liver injury (AST,ALT, GGT and bilirubin) ; electrochemiluminescence assay was performed to measure serum TPS level; immunohistochemistry staining was done to evaluate M30 immunoreactivity in hepatic tissue biopsy specimens and the apoptotic score was acquired. Then the correlations were analyzed between various indices and the apoptotic scores. Results The serum TPS level was positively correlative to the hepatocyte apoptotic score in alcoholic hepatitis group; and their correlation coefficient was the largest among various liver functional indices and the apoptotic scores. The correlation coefficient between TPS level and apoptotic score was significantly higher in alcoholic hepatitis group than that in fatty liver group (P＜0.05). Conclusion Serum TPS may be used as a good hepatocyte apoptosis marker for alcoholic hepatitis, which contributes to the differential diagnosis of alcoholic hepatitis and fatty liver.

Effect of HCMV on expressions of K8 and K18 in duct epithelial cells of salivary gland / 中华微生物学和免疫学杂志

Objective To study the effect of human cytomegalovirus (HCMV) on expressions of K8 and K18 in duct epithelial cells of salivary gland. Methods The expressions of immediate early antigen of HCMV, K8 and K18 were detected by immunohistochemistry staining in tissues embedded in paraffin of parotid cytomegalic inclusion disease(PCID). Results Cytomegly bearing inclusion appeared in duct epithelium of PCID. DDG9/CCH2 antigen of HCMV was expressed in cytomegly bearing inclusion. K8 was negative in these cytomegly while K18 was intensively positive. Conclusion It is suggested that breaking down of K8 be induced in parotid duct epithelial cells infected by HCMV and that up-regulation of K18 may be a reactive change. Keratin network in simple epithelium functions to impart mechanical integrity to cells.